Background: Sarcoidosis is an immune-mediated inflammatory disease whose natural development is not well understood. We aimed to determine if inflammatory plasma protein levels are elevated before sarcoidosis diagnosis compared to controls. Furthermore, we investigated which proteins are increased and how long before diagnosis they are increased.
View Article and Find Full Text PDFTuberculosis (TB) and sarcoidosis are both granulomatous diseases. Here, we compared the immunological microenvironments of granulomas from TB and sarcoidosis patients using sequencing (ISS) transcriptomic analysis and multiplexed immunolabeling of tissue sections. TB lesions consisted of large necrotic and cellular granulomas, whereas "multifocal" granulomas with macrophages or epitheloid cell core and a T-cell rim were observed in sarcoidosis samples.
View Article and Find Full Text PDFFever is common among individuals seeking healthcare after traveling to tropical regions. Despite the association with potentially severe disease, the etiology is often not determined. Plasma protein patterns can be informative to understand the host response to infection and can potentially indicate the pathogen causing the disease.
View Article and Find Full Text PDFSarcoidosis incidence peaks in women between 50 and 60 years old, which coincides with menopause, suggesting that certain sex hormones, mainly estrogen, may play a role in disease development. We investigated whether menopausal hormone therapy (MHT) was associated with sarcoidosis risk in women and whether the risk varied by treatment type. We performed a nested case-control study (2007-2020) including incident sarcoidosis cases from the Swedish National Patient Register (n = 2593) and matched (1:10) to general population controls (n = 20,003) on birth year, county, and living in Sweden at the time of sarcoidosis diagnosis.
View Article and Find Full Text PDFBackground: Early identification of patients at risk for progressive sarcoidosis may improve intervention. High bronchoalveolar lavage fluid (BALF) lymphocytes and peripheral blood (PB) lymphopenia are associated with worse prognosis. The mechanisms behind are not disentangled, and to date, it is not possible to predict disease course with certainty.
View Article and Find Full Text PDFBackground: Sex differences in the susceptibility of sarcoidosis are unknown. The study aims to identify sex-dependent genetic variations in two clinical sarcoidosis phenotypes: Löfgren's syndrome (LS) and non-Löfgren's syndrome (non-LS).
Methods: A meta-analysis of genome-wide association studies was conducted on Europeans and African Americans, totaling 10,103 individuals from three population-based cohorts, Sweden ( = 3,843), Germany ( = 3,342), and the United States ( = 2,918), followed by an SNP lookup in the UK Biobank (UKB, = 387,945).
Sarcoidosis is an inflammatory granulomatous disease of unknown etiology involving any organ or tissue along with any combination of active sites, even the most silent ones clinically. The unpredictable nature of the sites involved in sarcoidosis dictates the highly variable natural history of the disease and the necessity to cluster cases at diagnosis based on clinical and/or imaging common characteristics in an attempt to classify patients based on their more homogeneous phenotypes, possibly with similar clinical behavior, prognosis, outcome, and therefore with therapeutic requirements. In the course of the disease's history, this attempt relates to the availability of a means of detection of the sites involved, from the Karl Wurm and Guy Scadding's chest x-ray staging through the ACCESS, the WASOG Sarcoidosis Organ Assessment Instruments, and the GenPhenReSa study to the F-FDG PET/CT scan phenotyping and far beyond to new technologies and/or the current "omics.
View Article and Find Full Text PDFObjective: The lung is implicated as a site for breach of tolerance prior to onset of seropositive rheumatoid arthritis (RA). To substantiate this, we investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from untreated early RA patients and anti-citrullinated protein antibody (ACPA)-positive individuals at risk for developing RA.
Methods: Single B cells (n = 7,680) were phenotyped and isolated from BAL samples from individuals at risk of RA (n = 3) and at RA diagnosis (n = 9).
Different human leukocyte antigen (HLA) alleles associate with disease phenotypes in sarcoidosis. Peripheral blood (PB) lymphopenia is reported as more common in sarcoidosis patients with worse prognosis. The mechanisms behind are unrecognized but a PB depletion due to lymphocytes migrating to lung and/or extra pulmonary organs has been suggested.
View Article and Find Full Text PDFObjective: We aimed to investigate whether obesity, tobacco use, alcohol consumption and physical inactivity are associated with sarcoidosis risk.
Methods: We conducted a matched case-control study nested within the Northern Sweden Health and Disease Study. Incident sarcoidosis cases (n=165) were identified medical records and matched to controls (n=660) on sub-cohort, sex, birth and questionnaire date (1:4).
Background: Sarcoidosis is an inflammatory disease that affects multiple organs. Cell analysis from bronchoalveolar lavage fluid (BALF) is a valuable tool in the diagnostic workup and differential diagnosis of sarcoidosis. Besides the expansion of lymphocyte expression-specific receptor segments (Vα2.
View Article and Find Full Text PDFThe CRISPR prime editor PE2 consists of a Streptococcus pyogenes Cas9 nickase (nSpCas9) fused at its C-terminus to a Moloney murine leukemia virus reverse transcriptase (MMLV-RT). Here we show that separated nSpCas9 and MMLV-RT proteins function as efficiently as intact PE2 in human cells. We use this Split-PE system to rapidly identify and engineer more compact prime editor architectures that also broaden the types of RTs used for prime editing.
View Article and Find Full Text PDFIncorrect medication administration causes millions of undesirable complications worldwide every year. The problem is severe and there are many control systems in the market, yet the exact molecular composition of the solution is not monitored. Here, we propose an alarm sensor based on UV-Vis spectroscopy and refractometry.
View Article and Find Full Text PDFBackground: Early detection and initiation of treatment in cardiac sarcoidosis (CS) is believed to be crucial to reduce morbidity and mortality. The diagnosis of CS is challenging, especially in isolated CS (ICS). Certain human leukocyte antigen (HLA-DRB1) alleles associate with different phenotypes of sarcoidosis.
View Article and Find Full Text PDFBackground: To address the reactivity and affinity against histidyl-transfer RNA synthetase (HisRS) autoantigen of anti-Jo1 autoantibodies from serum and bronchoalveolar lavage fluid (BALF) in patients with idiopathic inflammatory myopathies/anti-synthetase syndrome (IIM/ASSD). To investigate the associations between the reactivity profile and clinical data over time.
Methods: Samples and clinical data were obtained from (i) 25 anti-Jo1 patients (19 sera with 16 longitudinal samples and 6 BALF/matching sera at diagnosis), (ii) 29 anti-Jo1 patients (25 sera and 4 BALF/matching sera at diagnosis), and (iii) 27 age/gender-matched healthy controls (24 sera and 3 BALF/matching sera).
Background: The mineralocorticoid hormone aldosterone is a key regulator of the sodium-potassium balance and blood pressure. In excess, aldosterone relates to hypertension and cardiovascular disease (CVD). Here, we systematically investigated aldosterone secretion during the day in terms of salivary aldosterone awakening response (AldAR) and salivary aldosterone daytime levels (AldDay) under controlled conditions in participants' natural environment including assessment of potential confounding variables.
View Article and Find Full Text PDFBackground: Sarcoidosis incidence peaks in females around the fifth decade of life, which coincides with menopause, suggesting hormonal factors play a role in disease development. We investigated whether longer exposure to reproductive and hormonal factors is associated with reduced sarcoidosis risk.
Methods: We conducted a matched case-control study nested within the Mammography Screening Project.
In the past two decades, an increasing body of studies has been published on the intersex phenomenon in separate-sexed crustaceans from marine and freshwater ecosystems. Various causes are being considered that could have an influence on the occurrence of intersex. Besides genetic factors, environmental conditions such as photoperiodicity, temperature, salinity and parasitism, but also environmental pollution with endocrine disrupting chemicals (EDCs) are discussed.
View Article and Find Full Text PDFBackground: Sarcoidosis is an elusive disease due to its heterogeneity. It is well recognized that the clinical picture is dependent on ethnicity, organ involvement and age. However, data on the role of sex is inconsistent.
View Article and Find Full Text PDFDue to conflicting findings in previous studies, it remains unclear whether individuals with sarcoidosis are at a higher relative risk of acute myocardial infarction. In this cohort study, individuals with sarcoidosis and matched general population comparators were followed for acute myocardial infarction in Swedish nationwide registers. A small (20%) risk increase associated with sarcoidosis was identified, which did not markedly vary by age at diagnosis, sex, treatment status around diagnosis, and time since diagnosis.
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